Metabolic trapping
The tracer rides in on the transporter for a real metabolite, gets modified by the pathway’s first enzyme, and is then stranded — charged enough that it cannot leave, altered enough that the next enzyme will not touch it.
This is the largest single family and the one with the most exam traps, because retention depends on the ratio of two enzymes, not on one. Hexokinase phosphorylates and traps; glucose-6-phosphatase reverses it and releases. Tissues rich in the reversing enzyme — hepatocytes above all — clear the tracer, which is why liver background is moderate and why well-differentiated hepatocellular carcinoma is so often FDG-cold.
Everything that competes for the transporter degrades the study. Serum glucose competes with FDG, and the insulin released after a meal drives tracer into muscle and fat; those are the reasons for the fasting requirement, not radiation safety or comfort.
The agents
F-18 FDGfluorodeoxyglucose
PETF-18 · t½ 110 min · β⁺ 634 keV max · 511 keV annihilation
- Handle
- GLUT1/GLUT3 transporters, then hexokinase
- Trapping
- Phosphorylated to FDG-6-phosphate. The negative charge blocks efflux; the 2-fluorine blocks isomerisation. Retention ∝ (transport × hexokinase) ÷ glucose-6-phosphatase.
- Use
- Oncologic staging and response, infection and FUO, epilepsy focus (interictal hypometabolism), myocardial viability, large-vessel vasculitis, sarcoidosis.
- Pitfall
- Hyperglycaemia competes — fast 4–6 h, target glucose under ~150–200 mg/dL. Brown fat, muscle, post-treatment marrow and thymic rebound, granulomas and infection are all avid. False negatives in mucinous, low-grade, prostate, renal cell, well-differentiated HCC (high G6Pase) and small lesions. Brain background is high — a cerebral metastasis can hide.
F-18 FLTfluorothymidine · research
PETF-18 · t½ 110 min
- Handle
- Thymidine kinase 1 (salvage pathway, S-phase)
- Trapping
- Phosphorylated to FLT-monophosphate and trapped. It is a poor substrate for DNA polymerase, so it is not incorporated into DNA — it images proliferative capacity, not DNA synthesis itself.
- Use
- Proliferation imaging; early response assessment in trials, where it changes before size does.
- Pitfall
- Intense physiologic marrow and liver uptake (hepatic glucuronidation) limits abdominal reads. Absolute uptake is far lower than FDG, so lesion contrast is poor. Not FDA-approved.
C-11 choline / F-18 fluorocholineC-11 choline is FDA-approved
PETC-11 · t½ 20.4 min (on-site cyclotron) · F-18 analogue t½ 110 min
- Handle
- Choline transporters, then choline kinase
- Trapping
- Phosphorylated to phosphocholine and committed to phosphatidylcholine synthesis — trapped by the demand for new cell membrane rather than by energy demand.
- Use
- Recurrent prostate cancer with a non-informative bone scan and CT; hepatocellular carcinoma and parathyroid in some centres.
- Pitfall
- Largely displaced by PSMA PET. Marked liver, pancreas and kidney uptake; inflammatory nodes are avid. Advantage over FDG, for C-11 choline, is the low urinary excretion, which keeps the prostate bed readable; F-18 fluorocholine is excreted in urine, so early pelvic imaging is used.
N-13 ammonia—
PETN-13 · t½ 9.96 min · on-site cyclotron required
- Handle
- Free diffusion as NH₃, then glutamine synthetase
- Trapping
- Diffuses into the myocyte, then is converted to N-13 glutamine and trapped. Extraction ~80%, near-linear with flow to about 2.5 mL/min/g before rolling off.
- Use
- Myocardial perfusion PET with absolute blood flow and flow reserve; the most accurate widely available flow agent.
- Pitfall
- Liver and lung activity can obscure the inferior wall. Increased lung uptake suggests raised LV filling pressure. The 10-minute half-life makes it a cyclotron-site agent only.